Pat1 RNA‐binding proteins: Multitasking shuttling proteins

Abstract

Post-transcriptional regulation of gene expression is largely achieved at the level of splicing in the nucleus, and translation and mRNA decay in the cytosol. While the regulation may be global, through the direct inhibition of central factors, such as the spliceosome, translation initiation factors and mRNA decay enzymes, in many instances transcripts bearing specific sequences or particular features are regulated by RNA-binding factors which mobilize or impede recruitment of these machineries. This review focuses on the Pat1 family of RNA-binding proteins, conserved from yeast to man, that enhance the removal of the 5 0 cap by the decapping enzyme Dcp1/2, leading to mRNA decay and also have roles in translational repression. Like Dcp1/2, other decapping coactivators, including DDX6 and Edc3, and translational repressor proteins, Pat1 proteins are enriched in cytoplasmic P-bodies, which have a principal role in mRNA storage. They also concentrate in nuclear Cajalbodies and splicing speckles and in man, impact splice site choice in some pre-mRNAs. Pivotal to these functions is the association of Pat1 proteins with distinct heptameric Lsm complexes: the cytosolic Pat1/Lsm1-7 complex mediates mRNA decay and the nuclear Pat1/Lsm2-8 complex alternative splicing. This dual role of human Pat1b illustrates the power of paralogous complexes to impact distinct processes in separate compartments. The review highlights our recent findings that Pat1b mediates the decay of AU-rich mRNAs, which are particularly enriched in P-bodies, unlike the decapping activator DDX6, which acts on GC-rich mRNAs, that tend to be excluded from P-bodies, and discuss the implications for mRNA decay pathways. This article is categorized under: RNA Turnover and Surveillance > Regulation of RNA Stability RNRNA Processing > Splicing Regulation/Alternative Splicing Translation > Translation Regulation K E Y W O R D S3 0 -5 0 decay, 5 0 -3 0 decay, alternative splicing, deadenylation, RNA processing

Mutations in genes encoding regulators of mRNA decapping and translation initiation: links to intellectual disability

“…In terms of function, DDX6 proteins have been characterized as enhancers of decapping and as repressors of translation, as reviewed in [ 47 ]. These roles are mediated by their interaction with DCP1–DCP2 as well as the decapping activators EDC3, PAT1B and LSM1–7 proteins on the one hand [ 33 , 34 , 48 , 49 ], and with translational repressor factors such as 4E-T, which sequesters the cap-binding translation initiation factor eIF4E, and LSM14, on the other [ 48 , 50–53 ]. Additional interactors of note include the CCR4-NOT deadenylase subunit CNOT1, whose binding enhances DDX6 ATPase activity to promote miRNA-mediated translational repression [ 19 , 51 , 54 , 55 ] ( Figure 2 ).…”

RNA sequencing of blood in coronary artery disease: involvement of regulatory T cell imbalance

“…Likewise, EDC3 is considered an important regulator of mRNA translation and decay [ 70 ], and interestingly, DDX proteins (i.e. DDX6) are known partners to EDC3 and mRNA decapping enzymes in the regulation of P-body assembly and function [ 71 ]. Of note is the Lamin A (LMNA) transcript, which is the target of germline mosaic mutations in Hutchinson-Guilford Progeria, a premature aging syndrome characterized by aggressive atherosclerosis and myocardial infarction in adolescents [ 72 ].…”

Roles of the pro-apoptotic factors CaNma111 and CaYbh3 in apoptosis and virulence of Candida albicans

“…We suggest that CaDhh1, CaEdc3, and CaPat1 could all participate in apoptosis, with each playing a distinct role. CaDhh1 and CaPat1 show protein interactions with each other but differ in their functional domains, intracellular locations, and mRNA targets 20 , 34 .…”